It’s a curious fact that when you remove the spleens of old mice, they live longer.1

Like, by a lot. Mice that were splenectomized at 2 years old (which is elderly for a mouse) had a median lifespan 19% longer than control mice, and a whopping 34% longer than sham-operated mice.

This doesn’t mean you should go get your spleen removed. You need your spleen; people who get splenectomies or who have inadequate spleen function are at greater risk for infection, because the spleen is full of macrophages which destroy bacteria and memory B cells which produce antibodies. And abdominal surgery in otherwise healthy people is almost never a good risk-benefit tradeoff.

But it’s intriguing. If removing aged spleens can extend life, is there something that the aged spleen is producing that’s bad for you?

Well, what’s different about young and old spleens?

Aged spleens are smaller than young spleens.2 They have 1/8 of the volume of white pulp (the lymphoid tissue, full of lymphocytes) but 27 times as much volume of red pulp (which is mostly connective tissue, blood cells, and specialized macrophages which eat damaged blood cells.)

And aged spleens have fewer of every type of cell except mast cells, which are much more abundant.

Could mast cells be the culprit?

Let’s look at another angle: the Tabula Muris Senis, a database which compares single-cell gene expression of mice at various ages. Which cell types are more common in aged spleens than young spleens? Which genes are expressed more in aged than young spleens?

• There’s significantly more erythroblasts after 24 months

• There’s significantly more granulocytes (which include mast cells) after 24 months

• There’s significantly more megakaryocyte-erythroid progenitor cells after 24 months

• There’s significantly more plasma B cells at 30 months

• The genes whose expression rose the most between 3-18 months and 24-30 months are:

  • Beta-s, found mostly in erythroblasts and megakaryocyte-erythroid progenitor cells;

  • S100a8 and S100a9, the two subunits of calprotectin, an inflammatory marker found at its highest levels in granulocytes and also in erythroblasts and megakaryocyte-erythroid progenitor cells;

  • Camp, the gene for cathelicidin, mostly found in granulocytes and used to attack bacteria;

  • Ngp, or neutrophilic granule protein, mostly found in granulocytes

So this is consistent with a picture where granulocytes and granulocyte-specific genes rise in abundance with age.

So what are granulocytes/mast cells doing in the spleen?

Mast cells release lots of pro-inflammatory signals when activated by an IgE antibody. They are responsible for allergic responses. Usually they hang out near blood vessels and the mucosa of the